57 articles - From Friday Aug 26 2022 to Friday Sep 02 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
| Thromb Haemost |
Concomitant use of selective serotonin reuptake inhibitors and oral anticoagulants and risk of major bleeding: a systematic review and meta-analysis. Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding. Overall, our findings suggest that physicians may need to tailor treatment according to individual patient risk factors for bleeding when prescribing SSRIs to patients using OACs. |
RCT, clinical trials, retrospective studies, etc…
| Blood |
A UNIQUE IMMUNE SIGNATURE IN BLOOD SEPARATES THERAPY-REFRACTORY FROM THERAPY-RESPONSIVE ACUTE GRAFT-VERSUS-HOST DISEASE. In these non-responding patients, effector and regulatory T-cells with skin/gut homing receptors also remained proportionally high over time, while their frequencies declined in therapy responders. Our results underscore the additive value of high dimensional immune cell profiling for clinical response evaluation, which may assist timely decision making in the management of severe aGvHD. |
Chronic Conditions, Late Mortality and Health Status After Childhood AML: A Childhood Cancer Survivor Study Report. Self-reported health status was good to excellent for 88.2% of survivors, regardless of treatment; however, this was lower than siblings (94.8%; p<0.0001). Although HCT is associated with greater long-term morbidity and mortality compared with chemotherapy-based treatment, these gaps have narrowed and al treatment groups report favorable health status. |
Conformation of von Willebrand factor in shear flow revealed with stroboscopic single-molecule imaging. Modeling VWF with a Brownian dynamics simulation, our results are consistent with VWF behaving as an uncollapsed polymer rather than the theorized compact ball. The muted response of free VWF to high shear rates implies that 1) the tension experienced by free VWF in physiological shear flow is lower than indicated by previous reports and 2) that tethering to platelets or the vessel wall is required to mechanically activate VWF adhesive function for primary hemostasis. |
Engineering T cells to suppress acute GvHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation. Further, combining OX40 targeting with a leukemia-specific chimeric antigen receptor (CAR) in a single T-cell product provides simultaneous protection against leukemia and acute GvHD in a mouse xenograft model of residual disease post-transplant. These results underscore the central role of OX40+ T-cells in mediating acute GvHD pathogenesis and support the feasibility of a bi-functional engineered T-cell product derived from the stem cell donor to suppress both disease relapse and acute GvHD following allo-HSCT. |
Hypoxia and low temperature up-regulate transferrin to induce hypercoagulability at high altitude. Thus, low temperature and hypoxia up-regulated transferrin expression promoted hypercoagulability. Our data suggest that targeting the transferrin-coagulation pathway is a novel and may be a powerful strategy against thromboembolic events caused by harmful environmental factors under high-altitude conditions. |
Loss of a4A- and ß1-tubulin leads to severe platelet spherocytosis and strongly impairs hemostasis in mice. In conclusion, this study shows that blood platelets require two unique a- and ß-tubulin isotypes to acquire their characteristic discoid morphology. Lack of these two isotypes has a deleterious effect on flow-dependent aggregate formation and stability, leading to a severe bleeding disorder. |
Low-dose decitabine modulates myeloid-derived suppressor cell fitness via LKB1 in immune thrombocytopenia. In conclusion, our study suggests that the impaired aerobic metabolism of MDSCs is involved in the pathogenesis of ITP, and the modulatory effect of decitabine on MDSC metabolism contributes to the improvement of its immunosuppressive function. This provides a possible mechanism for sustained remission elicited by low-dose decitabine in patients with ITP. |
Normalization of cerebral hemodynamics following hematopoietic stem cell transplant in children with sickle cell disease. HSCT normalizes whole-brain hemodynamics following curative HSCT in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection following HSCT in this high-risk patient population. |
S100A8/A9 drives the formation of procoagulant platelets through GPIba. The effect of S100A8/A9 on platelets was abolished by recombinant GPIba ectodomain, platelets from Bernard-Soulier Syndrome patient with GPIb-IX-V deficiency and platelets from mice deficient in the extracellular domain of GPIba. In conclusion, we identified the S100A8/A9-GPIba interaction as a novel targetable prothrombotic pathway inducing procoagulant platelets and fibrin formation, in particular in diseases associated with high levels of S100A8/A9, such as COVID-19. |
| Blood Adv |
A tumor volume and performance status model to predict outcome prior to treatment in diffuse large B-cell lymphoma. The combination of high TMTV >220 cm3 and ECOG-PS>=2 is a simple clinical model to identify pretreatment aggressive LBCL-risk categories. This combination addresses the unmet need to better predict before treatment initiation for aggressive LBCL, those patients likely to benefit the most or not at al from therapy. |
Absence of hyperfibrinolysis may explain lack of efficacy of tranexamic acid in hypoproliferative thrombocytopenia. TXA trough concentrations were highly variable (range: 0.7-10 ug/ml) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, -0.78) or tPA-CLT (r, 0.74). We conclude: 1] No evidence of fibrinolytic activation was observed in these thrombocytopenic patients; 2] trough TXA concentrations varied significantly between patients receiving the same dosing schedule; and 3] tPA-CLT and PG correlated well with TXA drug levels. |
Deferiprone for transfusional iron overload in sickle cell disease and other anemias: open-label study of up to 3 years. In conclusion, long-term therapy with deferiprone was not associated with new safety concerns and led to continued and progressive reduction in iron load in individuals with SCD or other anemias. #NCT02443545. |
Human acute leukemia utilizes branched-chain amino acid catabolism to maintain stemness through regulating PRC2 function. Inhibition of BCAA catabolism in primary AML or ALL cells specifically inactivates polycomb repressive complex 2 (PRC2) function, an epigenetic regulator for stem cell signatures, through inhibiting transcription of PRC components, such as zeste homolog 2 (EZH2) and embryonic ectoderm development (EED). Accordingly, BCAA catabolism plays an important role in maintenance of stemness in primary human AML and ALL, and molecules related to the BCAA metabolism pathway should be critical targets for acute leukemia treatment. |
Impact of mesenchymal stromal cell-derived vesicular cargo on B-cell acute lymphoblastic leukemia progression. Consistently, human trephine biopsies of patients with B-ALL showed a reduced percentage of PLEKHM1+ MSC. In summary, our data reveal an important role of BMM-derived sEV for driving specifically BCR-ABL1+ B-ALL, possibly contributing to its worse prognosis compared to BCR-ABL1- B-ALL, and suggest that secretion of inflammatory cytokines by cancer cells in general may similarly modulate the tumor microenvironment. |
Prolonged XPO1 inhibition is essential for optimal antileukemic activity in NPM1-mutated AML. Eltanexor caused irreversible HOX downregulation, induced terminal AML differentiation and prolonged survival of leukemic mice. This study provides essential information for the appropriate design of clinical trials with XPO1 inhibitors in NPM1-mutated AML. |
Rational polypharmacological targeting of FLT3, JAK2, ABL, and ERK1 suppresses the adaptive resistance to FLT3 inhibitors in AML. Pluripotin treatment curbed the progression of AML in multiple in vivo models including patient-derived primary AML cells in mouse xenotransplants. As a proof of concept, we demonstrate that targeted polypharmacological inhibition of key signaling nodes driving adaptive resistance can provide a durable response. |
Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: results from the phase Ib PORTIA study. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159). |
Sequencing T-cell redirection therapies leads to deep and durable responses in relapsed/refractory myeloma patients. T-cell redirection therapy as first or second salvage was feasible and associated with a median PFS1 of 28.9 months and PFS2 of 30.9 months and an OS of 62% at 2 years. Sequential use of different T-cell redirection therapies is possible and can lead to deep and durable responses following relapse after BiAb therapy in RRMM. |
Temporal in vivo platelet labelling in mice reveals age-dependent receptor expression and conservation of specific mRNAs. Our pulse-chase type approach to define circulating platelet age has allowed timely re-examination of commonly held beliefs regarding size and reactivity of young platelets whilst providing novel insights into the temporal regulation of receptor and protein expression. Overall, future application of this validated tool will inform on age-based platelet heterogeneity in physiology and disease. |
| Haematologica |
ATRA works synergistically with the Taken together, the data show that ATRA treatment leads to enhanced BCMA expression on MM cells and consecutively, enhanced reactivity of BCMA-CAR T-cells. The data support the clinical evaluation of ATRA in combination with BCMA-CAR T-cell therapy and potentially, other BCMA-directed immunotherapies. |
| J Hematol Oncol |
Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL. Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration. |
| Lancet Haematol |
Luspatercept for the treatment of anaemia in non-transfusion-dependent ß-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial. Interpretation Luspatercept represents a potential treatment for adult patients with non-transfusion-dependent ß-thalassaemia, for whom effective approved treatment options are scarce. Funding Celgene and Acceleron Pharma. |
| Leukemia |
A senescence stress secretome is a hallmark of therapy-related myeloid neoplasm stromal tissue occurring soon after cytotoxic exposure. Finally, sequential patient sampling showed senescence phenotypes are induced within months of cytotoxic exposure, well prior to the onset of secondary cancer. Our data underscores a role of senescence in the pathogenesis of tMN and provide a valuable resource for future therapeutics. |
Concurrent Zrsr2 mutation and Tet2 loss promote myelodysplastic neoplasm in mice. Collectively, this study shows that concomitant Zrsr2 mutation and Tet2 loss are sufficient to initiate MDS in mice. Understanding this mechanistic interplay will be crucial for the identification of novel therapeutic targets in the spliceosome/epigenetic MDS subgroup. |
Epigenomic profiling of glucocorticoid responses identifies cis-regulatory disruptions impacting steroid resistance in childhood acute lymphoblastic leukemia. By integrating our GC response maps with genetic and epigenetic datasets in primary ALL cells from patients, we further uncovered cis-regulatory disruptions at GC-responsive genes that impact GC resistance in childhood ALL. Overall, these data indicate that GCs initiate pervasive effects on the leukemia epigenome, and that alterations to the GC gene regulatory network contribute to GC resistance. |
Loss of AID exacerbates the malignant progression of CLL. Notably, CLL cells from patients with IgHV-unmutated disease express higher levels of XBP1s mRNA compared to those from patients with IgHV-mutated CLL. Our studies thus reveal novel mechanisms by which the loss of AID leads to worsened CLL and may explain why unmutated CLL is more aggressive than mutated CLL. |
Prediction of thrombosis in post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a study on 1258 patients. Considering individually cytoreductive therapies, univariate regression model found that both conventional cytoreduction, mainly hydroxyurea, (HR 0.41, 95% CI: 0.26-0.65, p |
| Thromb Haemost |
Clinical Complexity Domains, Anticoagulation, and Outcomes in Patients with Atrial Fibrillation: A Report from the GLORIA-AF Registry Phase II and III. In AF patients, clinical complexity influences OAC treatment management, and increases the risk of poor clinical outcomes. These patients require additional efforts, such as integrated care approach, to improve their management and prognosis. |
Essen Stroke Risk Score Predicts Clinical Outcomes in Heart Failure Patients With Preserved Ejection Fraction: Evidence From the TOPCAT trial. The ESRS had modest discriminatory abilities for predicting stroke as well as other adverse outcomes including myocardial infarction, hospitalization, and death in HFpEF patients. Furthermore, ESRS might have improvement in clinical usefulness compared with other scores in patients at high risk for stroke. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| J Hematol Oncol |
Connecting telomere maintenance and regulation to the developmental origin and differentiation states of neuroblastoma tumor cells. This review summarizes recent advances in the characterization of telomere structure and telomere maintenance mechanisms in neuroblastoma and discusses the findings in the context of relevant literature on telomeres during embryonic and neural development. Understanding the canonical and non-canonical roles of telomere maintenance in neuroblastoma could reveal vulnerabilities for telomere-directed therapies with potential applications to other pediatric malignancies. |
Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy. We discuss ongoing strategies targeting the myeloid compartment in the preclinical and clinical settings which include: (1) altering myeloid cell composition within the TME; (2) functional blockade of immune-suppressive myeloid cells; (3) reprogramming myeloid cells to acquire pro-inflammatory properties; (4) modulating myeloid cells via cytokines; (5) myeloid cell therapies; and (6) emerging targets such as Siglec-15, TREM2, MARCO, LILRB2, and CLEVER-1. There is a significant promise that myeloid cell-based immunotherapy will help advance immuno-oncology in years to come. |
Posttranslational control of lipogenesis in the tumor microenvironment. Underlying these abnormal metabolic behaviors are posttranslational modifications (PTMs) of lipid metabolism-related enzymes and other factors that can impact their activity and/or subcellular localization. This review focuses on the roles of these PTMs and specifically on how they permit the re-wiring of cancer lipid metabolism, particularly within the context of the tumor microenvironment. |
Recent advances in therapeutic strategies for triple-negative breast cancer. In addition, immunotherapy has also been demonstrated to improve overall survival and response in TNBC. In this review, we summarize recent key advances in therapeutic strategies based on molecular subtypes in TNBC. |
Treatment of myelodysplastic syndromes in the era of precision medicine and immunomodulatory drugs: a focus on higher-risk disease. Here, we review the most recent advances in therapeutic approaches in MDS, focusing on higher-risk disease. Allogeneic hematopoietic cell transplantation is beyond the scope of this article. |
| Leukemia |
Current status and future perspectives in targeted therapy of NPM1-mutated AML. We also discuss the current therapeutic results obtained in NPM1-mutated AML with the BCL-2 inhibitor venetoclax and the preliminary clinical results using menin inhibitors targeting HOX/MEIS1 expression. Finally, we review various immunotherapeutic approaches in NPM1-mutated AML, including immune check-point inhibitors, CAR and TCR T-cell-based therapies against neoantigens created by the NPM1 mutations. |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Haematologica |
| Lancet Haematol |
Letters to the editors and authors’ replies
| J Hematol Oncol |
Comparative analysis of cancer cell responses to targeted radionuclide therapy (TRT) and external beam radiotherapy (EBRT). In vivo, EGFR inhibitor erlotinib increased therapeutic response to [ 177 Lu]Lu-PP-F11N and median survival of A431/CCKBR-tumor bearing nude mice. In summary, our study explores a complex scenario of cancer responses to different types of irradiation and pinpoints the radiosensitizing strategy, based on the targeting survival pathways, which are activated by TRT. |
Osteosarcoma with cell-cycle and fibroblast growth factor genomic alterations: case report of Molecular Tumor Board combination strategy resulting in long-term exceptional response. Treatment was given at reduced dosing (lenvatinib 10 mg oral daily (approved dose |
| Leukemia |